1. Field of the Invention
This invention relates generally to diabetes-mediating proteins, methods of identifying diabetes-mediating proteins, transgenic animals useful in the assays of the invention, methods for screening for drugs which affect the expression of diabetes-mediating proteins, and therapeutic compounds for the treatment and prevention of diabetes.
2. Related Art
The development of insulin-dependent diabetes mellitus (IDDM) in man, and in animal models of human disease, is characterized by mononuclear cell infiltration and, β-cell destruction in the pancreatic islets (insulitis). The mechanisms behind β-cell destruction is not known. Accumulating evidence indicates that the cytokine interleukin-1,6 (IL-1β), primarily produced by macrophages and monocytes, may be a mediator of islet, β-cell destruction.
Animal models of human diabetes include diabetes-prone BB (BB-DP) rats and non-obese diabetic (NOD) mice. 2-Dimensional (2D) gel maps of rat islet proteins have been constructed and used to determine qualitative and quantitative changes in protein synthesis resulting with in vitro exposure of rat islet cells to IL-1β (Andersen et al. Diabetes 44:400-407 (1995)).
Transgenic animal models of human diseases are known. For example, one model for human diabetes is a transgenic mouse expressing a viral protein in the pancreatic β cells under control of the rat insulin promoter (van Herrath et al. J. Clin. Invest. 98:1324-1331 (1996)). Less than 2% of the transgenic mice develop diabetes spontaneously; however, after a 2 month challenge with the virus, IDDM occurs in more than 95% of the mice.